It has been reported that approximately 50% of patients in developed countries do not take their medications as prescribed, that complex drug regimen is a factor contributing to poor medication adherence, and that adherence lies between treatment and outcomes.
Non-adherence to medicines is estimated to cost the health care system $100 billion-$300 billion per year, and numerous studies have shown that high rates of non-adherence directly relates to poor clinical outcomes. Further, simple dosing, for example one pill per day, helps maximize adherence, and medicines that lower the number of pills per day help eliminate some of the known barriers to adherence.
Compound 1 is a small molecule active pharmaceutical ingredient in clinical development stage for the treatment of sickle cell disease, pulmonary disease such as idiopathic pulmonary fibrosis, and hypoxia and hypoxemia conditions. The clinical doses of Compound 1, in adults, can be considered high. Clinical doses include Compound 1 in the range of 500 mg to 1000 mg, or up to 1500 mg, administered orally once a day in either 100 or 300 mg capsules. The high dose 300 mg capsules are Size 0 HPMC capsules and contain over 80% of Compound 1. For example, a size 0 capsule measures 21.6 mm length×7.64 mm diameter and only 300 mg of Compound 1 drug can be loaded in to such a capsule. Therefore, for the capsule formulation, 300 mg is the maximum strength feasible due to the density characteristics and the fixed fill volume and dimensions of the Size 0 capsule shell used.
Thus, there is a need for developing a pharmaceutical formulation containing Compound 1 that is suitable for making alternative dosage forms such as tablets that contain varying amounts of higher doses of Compound 1 to minimize the number of pills to be swallowed by a patient (pill burden) per dose, has suitable size for ease of swallowing, and releases Compound 1 such that it leads to the desired therapeutic effect. Another important advantage of tablet formulations over the capsules is the ability to scale up to commercial volumes and use high speed manufacturing equipment while keeping low cost of goods. The present disclosure fulfills this and related needs.